We propose to investigate pancreatic endocrine function in juvenile-onset diabetics to ascertain whether the glucagon-producing alpha cells of the pancreatic islets share the primary defect of the beta cells in being unable to normally respond to circulating levels of glucose and certain other modulators. We plan to use a recently developed computerized artificial pancreas (Biostator, Ames Co.) to continuously monitor blood glucose in juvenile diabetics and keep their circulating glucose in the normoglycemic range throughout meals and in the basal state. After a variety of challenges with either fructose, epinephrine or mixed meals and in the presence or absence of small doses of somatostatin, islet cell function will be characterized both in the normalized and insulin deficient state. Endogenous beta cell function will be monitored with measurements of C-Peptide concentrations. These studies are designed to further elucidate the endocrine defect of the pancreatic islet cells and to evaluate various glucagon suppressive techniques as an adjunct to insulin therapy in diabetes mellitus. Graded doses of somatostatin will be studied in normals, obese patients, as well as in both adult-onset and juvenile diabetics to determine whether a selectively low dose of somatostatin may effectively improve postprandial hyperglycemia without provoking malabsorption in certain diabetics on conventional insulin replacement.